A. P. falciparum is sensitive to the plastid-specific drug, micrococcin, in the nanomolar range. The site of thiostrepton action is in the GTPase site of the large subunit rRNA. Our interest in the specificity of that drug led to test other drugs targeted to the GTPase site. We found that micrococcin, a bacterial product, is a far more sensitive inhibitor of parasite growth than thiostrepton. This drug has never been commercially available and was almost forgotten. The source of drug for the experiments was found in its discoverer?s residential refrigerator in England and the microbe that produced it was eventually tracked down as well. The IC50 of the drug is several fold lower than chloroquine when compared in culture but its affect in animals has yet to be tested. B. Thiostepton interaction induces a tertiary structure in 35kb plastid encoded rRNA that is similar to the interaction of the drug with eubacterial rRNA We have examined the 35kb-encoded ribosomal GTPase site in collaboration with David Draper at Johns Hopkins University. Dr. Draper and colleagues have developed the technology to study the tertiary structure of the GTPase center of ribosomes as well as the effect of drugs and proteins on such structures. We have investigated all GTPase centers found in the plastid and cytoplasmic RNAs of P. falciparum as well as the effect of Thiostrepton on each. Thiostrepton induces a tertiary structure in the 35 kb GTPase center similar to that seen in eubacterial rRNA even though the sequences maintain only about 60% sequence identity. A single point mutation in the 35 kb GTPase center removes thiostrepton-dependent tertiary structure formation. Drug interaction with bacterial rRNA sequence and drug sensitivity of the eubacteria are directly related. The correlation of thiostrepton-sensitive and -resistant phenotypes with physical parameters suggests thiostrepton resistance as a selectable marker for plastid transformation. C. Chimeric rRNAs containing the GTP?ase centers of the developmentally regulated ribosomal rRNAs of Plasmodium falciparum are functionally distinct. The human malaria parasite Plasmodium falciparum maintains at least two distinct types, A and S, of developmentally controlled ribosomal RNAs. To investigate specific functions associated with these rRNAs we replaced the Saccharomyces cerevisiae GTPase domain of the 25S rRNA with GTPase domains corresponding to the Plasmodium A- and S-type 28S rRNAs. The expression of either A- or S-type chimeric RNA in yeast increased translational accuracy. Yeast containing only A-type chimeric rRNA and no wild-type yeast rRNA grew at the wild-type level. In contrast, S-type chimeric rRNA severely inhibited growth in the presence of wild-type yeast rRNA, and caused lethality in the absence of the wild-type yeast rRNA. We show what before could only be hypothesized, that the changes in the GTPase center of ribosomes present during different developmental stages of Plasmodium species can result in fundamental changes in the biology of the organism.